Potential Roles for Estrogen Regulation of Telomerase Activity in Aging

Bayne, Sharyn Leanne; Jones, Morris; Li, He; Liu, Junping

doi:10.1196/annals.1396.023

Cited by 43 publications

(41 citation statements)

References 48 publications

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“…Fifty-three percent (nZ41) were cured after initial treatment and had no recurrence and 19.5% (nZ15) were cured after further therapies for recurrent disease. Fifteen cured patients (19.5%) were adrenal insufficient at the time of telomere analysis and required substitution therapy with hydrocortisone (mean dose 17.6G3.7 mg and range [10][11][12][13][14][15][16][17][18][19][20]. Nine patients (11.7%) were GH deficient (four of which were replaced with recombinant human GH (rhGH)); eight women (10.4%) were gonadotropin deficient (all on estrogen/progesterone hormone replacement therapy); and 15 patients (19.4%) were hypothyroid, ten due to thyroid-stimulating hormone (TSH) deficiency and five due to primary hypothyroidism (all on L-thyroxine (L-T 4 ) replacement).…”

Section: Subjectsmentioning

confidence: 99%

“…The time elapsed between both analyses was 40.1G15.6 months and mean time of remission was 28.5G14.1 months. Three cured patients (20%) were adrenal insufficient at the time of telomere analysis and required substitution therapy with hydrocortisone (mean dose 18.3G2.2 mg and range [10][11][12][13][14][15][16][17][18][19][20]; four patients (26.6%) were hypothyroid, two due to TSH deficiency and two due to primary hypothyroidism (all on L-T 4 replacement). None of the cured patients were GH-deficient; seven women (46.6%) were postmenopausal at remission, but no gonadotropin deficiency was observed (nZ8).…”

Section: Subjectsmentioning

confidence: 99%

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Telomere length analysis in Cushing's syndrome

Aulinas

Ramírez

Barahona

et al. 2014

European Journal of Endocrinology

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Introduction: Hypercortisolism in Cushing's syndrome (CS) is associated with increased morbidity and mortality. Hypercortisolism also occurs in chronic depressive disorders and stress, where telomere length (TL) is shorter than in controls. We hypothesized that shortening of telomere might occur in CS and contribute to premature aging and morbidity. Aim: To investigate TL in CS patients compared with controls. Methods: Seventy-seven CS patients (14 males, 59 pituitary, 17 adrenal, and one ectopic; 21 with active disease) were compared with 77 gender-, age-, and smoking-matched controls. Fifteen CS were evaluated longitudinally, during active disease and after remission of hypercortisolism. Leukocyte TL was measured by telomere restriction fragment-Southern technique. Clinical markers were included in a multiple linear regression analysis to investigate potential predictors of TL. Results: Mean TL in CS patients and controls was similar (7667 vs 7483 bp, NS). After adjustment for age, in the longitudinal evaluation, TL was shorter in active disease than after remission (7273 vs 7870, P!0.05). Age and dyslipidemia were negative predictors (P!0.05), and total leukocyte count was a positive predictor for TL (P!0.05). As expected, a negative correlation was found between TL and age (CS, RZK0.400 and controls, RZK0.292; P!0.05). No correlation was found between circulating cortisol, duration of exposure to hypercortisolism or biochemical cure and TL. Conclusion: Even though in the cross-sectional comparison of CS and controls no difference in TL was found, in the longitudinal evaluation, patients with active CS had shorter TL than after biochemical cure of hypercortisolism. These preliminary results suggest that hypercortisolism might negatively impact telomere maintenance. Larger studies are needed to confirm these findings.

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Section: Subjectsmentioning

confidence: 99%

Section: Subjectsmentioning

confidence: 99%

Telomere length analysis in Cushing's syndrome

Aulinas

Ramírez

Barahona

et al. 2014

European Journal of Endocrinology

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“…Among these genes, the proto-oncogene c-myc has been reported as a direct target gene of estrogen in estrogen receptor-positive cells [3]. Recently, studies have shown that estrogen stimulates the activity of the enzyme telomerase and gene expression of telomerase reverse transcriptase (TERT) in cancer cell cultures (reviewed in [4,5]). Telomerase is required to maintain the structures of chromosomal ends (telomeres) for continuous cell division in human embryonic development and cancer (reviewed in [6][7][8]).…”

Section: Introductionmentioning

confidence: 99%

Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice

Bayne

Jones

et al. 2008

Cell Res

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Estrogen deficiency mediates aging, but the underlying mechanism remains to be fully determined. We report here that estrogen deficiency caused by targeted disruption of aromatase in mice results in significant inhibition of telomerase activity in the adrenal gland in vivo. Gene expression analysis showed that, in the absence of estrogen, telomerase reverse transcriptase (TERT) gene expression is reduced in association with compromised cell proliferation in the adrenal gland cortex and adrenal atrophy. Stem cells positive in c-kit are identified to populate in the parenchyma of adrenal cortex. Analysis of telomeres revealed that estrogen deficiency results in significantly shorter telomeres in the adrenal cortex than that in wild-type (WT) control mice. To further establish the causal effects of estrogen, we conducted an estrogen replacement therapy in these estrogen-deficient animals. Administration of estrogen for 3 weeks restores TERT gene expression, telomerase activity and cell proliferation in estrogen-deficient mice. Thus, our data show for the first time that estrogen deficiency causes inhibitions of TERT gene expression, telomerase activity, telomere maintenance, and cell proliferation in the adrenal gland of mice in vivo, suggesting that telomerase inhibition and telomere shortening may mediate cell proliferation arrest in the adrenal gland, thus contributing to estrogen deficiency-induced aging under physiological conditions.

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“…It was proposed that the longer LTL in women compared with men stems from a slower rate of LTL attrition in premenopausal women, presumably because of estrogen-mediated stimulation of telomerase. 33 We recently showed in a longitudinal study that the rate of LTL attrition is in fact faster in premenopausal women than in postmenopausal women and that regardless of the menopausal status, age-adjusted LTL of women was longer than that of men. 34 Those findings suggested that the gender effect on LTL is established before adulthood.…”

Section: Figurementioning

confidence: 99%

Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease

Factor-Litvak¹,

Süsser

Kezios³

et al. 2016

Pediatrics

195

197

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BACKGROUND AND OBJECTIVE: In adults, leukocyte telomere length (LTL) is variable, familial, and longer in women and in offspring conceived by older fathers. Although short LTL is associated with atherosclerotic cardiovascular disease, long LTL is associated with major cancers. The prevailing notion is that LTL is a "telomeric clock, " whose movement (expressed in LTL attrition) reflects the pace of aging. Accordingly, individuals with short LTL are considered to be biologically older than their peers. Recent studies suggest that LTL is largely determined before adulthood. We examined whether factors that largely characterize LTL in adults also influence LTL in newborns.

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Potential Roles for Estrogen Regulation of Telomerase Activity in Aging

Cited by 43 publications

References 48 publications

Telomere length analysis in Cushing's syndrome

Telomere length analysis in Cushing's syndrome

Estrogen deficiency leads to telomerase inhibition, telomere shortening and reduced cell proliferation in the adrenal gland of mice

Leukocyte Telomere Length in Newborns: Implications for the Role of Telomeres in Human Disease

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